This study evaluates the effect of withdrawing amifampridine phosphate treatment from patients with LEMS. One half of the patients will continue to receive amifampridine phosphate and the other half will receive placebo, during this double-blind study.

This was a randomized (1:1), double-blind, placebo-controlled, parallel-group, withdrawal study designed to evaluate the efficacy and safety of amifampridine phosphate in patients diagnosed with LEMS. The study was planned to include approximately 28 male and female patients.

Prior to the study, patients were receiving unblinded treatment in the expanded access program (EAP-001). Patients had to be on a stable dose and frequency of amifampridine phosphate for at least 1 week prior to randomization into LMS-003. Screening and randomization (Day 0) may have been into a single visit.

Patients who met eligibility criteria were randomized 1:1 to amifampridine phosphate (at the patient's optimal dose) or placebo on Day 0.

Baseline assessments were obtained on Study Day 0, while the patient has been on open-label amifampridine phosphate and in relationship to the usual dosing schedule. Patients took blinded study medication on Day 1 through Day 3. On Day 4, a dose of blinded study medication was administered by the site study personnel. This was the same medication that the patient took on Day 1 through Day 3. The assessments listed below were performed following either the second, third, or fourth dose of medication taken on Day 4, and this should be the same dose after which Day 0 assessments were performed. For example, if the patient took their second dose of amifampridine in the clinic on Day 0 and had assessments started 40 minutes later, then on Day 4, that patient should be assessed after taking their second dose of investigational product (IP).

Beginning with the next dose after all Day 0 baseline assessments were completed, the patient received IP through Day 4, with a clinic visit on the last day (Day 4) for assessments.

The planned duration of participation for each patient was up to 12 days, including screening (up to 7 days), Day 0 assessments and randomization, and IP administration (Day 1 through Day 4).

Inclusion Criteria:

1. Male or female ≥18 years of age and currently receiving amifampridine phosphate for LEMS.
2. Diagnosis of LEMS by antibody testing or electromyography (EMG).
3. Completion of anti-cancer treatment at least 3 months (90 days) prior to Screening.
4. If receiving peripherally acting cholinesterase inhibitors (e.g. pyridostigmine), a stable dose of cholinesterase inhibitors is required for at least 7 days prior to randomization and throughout the study.
5. If receiving permitted oral immunosuppressants (prednisone or other corticosteroid), a stable dose is required for at least 30 days prior to randomization and throughout the study.
6. Female patients of childbearing potential must practice an effective, reliable contraceptive regimen during the study.
7. Able to perform all study procedures and assessments.
8. Willing and able to travel to study site and attend all clinic study visits.
9. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Clinically significant long corrected QT (QTc) interval on ECG in previous 12 months.
2. Seizure disorder.
3. Active brain metastases.
4. Unable to ambulate.
5. Pregnant or lactating females.
6. Any other condition which, in the opinion of the Investigator, might interfere with the patient's participation in the study or confound the assessment of the patient.

All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient).

Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.